The NIH-sponsored Training Program in Investigative Rheumatology, begun at Yale in 1976, has the philosophy that a portion of both M.D. and Ph.D. biomedical scientists should be trained in an environment that focuses upon mechanisms of rheumatologic and immunologic diseases, and approaches to the bedside investigation of these illnesses. This belief is grounded in the notion that the challenges involved in understanding such clinical problems require a cohort of investigators whose knowledge and training enable them to span the gaps between basic biology and clinical rheumatology and immunology. Hence, the goals of this program are to attract individuals who are interested in learning about fundamental mechanisms of disease and the applications of this knowledge. The program is focused upon clinical investigation in the rheumatic diseases, with an emphasis on providing training in immunology, microbiology, cellular and molecular biology, and the clinical sciences as applied to the understanding and therapy of rheumatic diseases; is comprised of both physician and Ph.D. trainees; and has for its training faculty a collaborative group of 36 physician and basic scientists from the Section of Rheumatology and other Sections in the Department of Medicine, and basic investigators from the Department of Immunobiology. The quality, cohesiveness, and diverse skills of these mentors, along with the skills and the desire of our trainees, are the most important requisites for success of our program. Five trainees (M.D. and Ph.D.) per year are currently supported, with an increase to six requested in this renewal. This request is based upon the continued success of the program and the number of high quality applicants and mentors. M.D. trainees typically perform clinical work in the first year of their fellowship (supported by clinical funds), and then enter research training. The combination of both M.D. and Ph.D. fellows gives the M.D. fellows a much better research experience, and it exposes the Ph.D. fellows to opportunities to apply their skills to rheumatologic problems. Fellows supported by this Training Grant receive didactic as well as interactive instruction in biology, clinical investigation, and ethical issues in science. This program provides trainees with the foundation in basic and clinical science that will enable them to bridge the differences between basic research and clinical approaches to understanding rheumatic diseases.